By taking advantage of the high activity of prostatic acid phosphatase (PAP) in prostatic epithelial cells and prostatic carcinoma cells in man and primates, we are designing agents that will become enzyme-activated to cytotoxic agents specifically by PAP. This has been made possible by the discovery that PAP can hydrolyze phosphates containing basic nitrogen, whereas other acid phosphatases are unable to do so. This is indicated by the determination of the P/K ratio (rate of hydrolysis by human prostate divided by that for human kidney). The other important parameter is the MTD ratio (maximum tolerated dose in the mouse, of the phosphate divided by the MTD of the unphosphorylated compound). To date we have prepared and examined nearly one hundred derivatives of the spindle poison Colchicine. We have identified two very promising derivatives for further examination. Currently, one is in the process of scale-up for examination in primates, while the other is readily available to large scale preparation. The initial primate studies are underway in stumptail monkeys. Work will continue to identify derivatives with higher P/K and MTD ratios in the screens and further observations of the two promising derivatives in primates as well as complete toxicity data will be compiled.